When the action of the enzyme tyrosinase within melanocytes (pigment-forming cells) is activated abnormally due to ultraviolet rays, hormonal imbalance or psychological stress and so forth, formation of melanin pigment is enhanced and they are successively sent out to surrounding epidermal cells. If the rate at which melanin pigment is produced is excessively fast and turnover is no longer normal due to the effects of ultraviolet rays and so forth, the melanin pigment is unable to be excreted to the outside and remains in the skin, and this is believed to result in the formation of spots in the skin.
Once a spot has been formed, it is preferably to treat the spot as quickly as possible, and a visual sensory evaluation of the spot by a beautician, or an early assessment of the presence of a spot by a quantitative evaluation of the spot using equipment such as an apparatus for capturing images of skin condition or a calorimeter, is desired for the purpose of providing treatment (Japanese Unexamined Patent Publication No. 2003-144393).
Once a spot being formed, it is not easily removed, and treatment is required that improves skin metabolism to quickly expel the unnecessary melanin and prevent excess melanin from being formed. Thus, it is preferably to care for the skin prior to the formation of a spot. However, since there are individual differences in susceptibility to spot formation and there are various conditions that cause their formation, it is typically difficult to predict the formation of a skin spot. Accordingly, a means for predicting whether or not the skin is susceptible to spot formation prior to formation thereof would be extremely effective as a preventive measure.
There is a report describing an attempt to evaluate the ease of formation of skin spots by collecting samples from sites of normal epidermis and using as an indicator thereof the detection of NT-3, ADAM9 or HB-EGF at each site (Japanese Unexamined Patent Publication No. 2003-245097). In addition, there is also a report describing an attempt to prevent the formation of skin spots by inhibiting c-KIT and ET (Japanese Unexamined Patent Publication No. 2004-83551). However, in addition to the complex pathological reactions in the body involved in the formation of skin spots not being completely understood, under the present circumstances in which a plurality of pigment synthesis stimulation pathways are known, there is still concern as to whether a definitive solution can be achieved in the case of judging the formation of skin spots or treating it by only focusing on a small number of genes. Therefore, a report has been published describing the detection of variations in a wide range of genes and using those genes as indicators for diagnosis (Japanese Unexamined Patent Publication No. 2004-205246). However, this report describes the detection of genes varying due to exposure of the skin to sunlight using a method referred to as SAGE, thus resulting in the need for the establishment of diagnostic and accommodation methods based on a wide-ranging analysis of skin spots per se.
Therefore, we determined a chronic inflammatory state characteristic of the sites of skin spots by comparing spot sites and normal sites of skin spot model mice using a microarray (Japanese Unexamined Patent Publication Nos. 2005-106475 and 2005-110505). The inventors of the present invention have now found acceleration of sebaceous gland-associated genes and inhibition of cornification-associated genes at spot sites in addition to the characteristic described above by comparing sites of age spots with normal sites, which are one of the typical skin spots found in humans.